Relaxin alone and in conjunction with interferon-gamma decreases collagen synthesis by cultured human scleroderma fibroblasts.
Relaxin alone and in conjunction with interferon-gamma decreases collagen synthesis by cultured human scleroderma fibroblasts.
复制标题
单独使用松弛素以及与干扰素-γ联合使用可降低培养的人硬皮病成纤维细胞的胶原蛋白合成。
DOI：
10.1111/1523-1747.ep12616665
复制
发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Amento,EP
中科院分区：
文献类型：
--
作者：
Unemori,EN;Bauer,EA;Amento,EP
来源于硬皮病患者受累皮肤的成纤维细胞在培养时经常表现出异常胶原表达的表型。来自7名患者的显示这种表型的成纤维细胞分别接受松弛素（1-100 ng/ml）和干扰素-γ (1-100 U/ml)单独或联合治疗，以评估这些细胞因子下调胶原合成和分泌的相对能力。硬皮病成纤维细胞对松弛素和干扰素-γ表现出不同的敏感性。与未处理的培养物相比，松弛素（100 ng/ml）降低了7个细胞系中6个细胞系胶原蛋白的表达，从8%到59%。干扰素-γ (100 U/ml)对所有7种细胞系的胶原分泌均有7%至89%的抑制作用。当松弛素和干扰素-γ联合使用时，松弛素增强IFN-γ诱导的7个细胞系中4个细胞系的胶原分泌减少。在其中的三条线中，松弛素与次优剂量的干扰素-γ联合使用导致的减少相当于或大于10倍浓度的干扰素-γ。本研究证明松弛素能够直接改变硬皮病成纤维细胞过度胶原生成的表型。此外，在某些情况下，松弛素和干扰素-γ联合使用可协同降低硬皮病细胞的胶原表达。
Fibroblasts derived from the involved skin of scleroderma patients frequently display a phenotype of supernormal collagen expression when cultured. Fibroblasts displaying this phenotype derived from seven patients were treated with relaxin (1–100 ng/ml) and interferon-γ (1–100 U/ml), individually and in combination, to assess the relative abilities of these cytokines to down-modulate collagen synthesis and secretion. Scleroderma fibroblasts displayed varying sensitivities to both relaxin and interferon-γ. Relaxin (100 ng/ml) decreased expression of collagen by six of seven lines tested from 8 to 59% compared to untreated cultures. Interferon-γ (100 U/ml) depressed collagen secretion by all seven lines in a range from 7 to 89%. When relaxin and interferon-γ were used in combination, relaxin augmented IFN-γ-induced decreases in collagen secretion in four of seven lines. In three of these lines, the use of relaxin in conjunction with suboptimal doses of interferon-γ resulted in decreases equivalent to or greater than that seen with a tenfold higher concentration of interferon-γ. This study demonstrates the ability of relaxin to directly alter the excessive collagen-producing phenotype of scleroderma fibroblasts. In addition, in some cases, combining relaxin and interferon-γ resulted in a cooperative effect in decreasing collagen expression by scleroderma cells in vitro.